Since serotonin (5-HT) synapse has been implicated to be an important site of action of antidepressant drugs, we have searched for a cultured cell system that can be used as a model to study the interactions between recognition sites for antidepressant drugs and receptors for 5-HT. We have found that 5-HT sensitive adenylate cyclase located in NCB-20, a hybrid cell line, can be effectively blocked by ketanserin (with a Ki = 50 nM) which is a selective antagonist for 5-HT2 receptors. The membrane preparation of NCB-20 cells also possesses high affinity binding sites for ketanserin, and mianserin, an atypical antidepressant. The binding parameters for ketanserin and mianserin are comparable to those reported in the membrane preparation of rat brain. In addition this cell line is equipped with a serotonin uptake system which is partially sodium dependent and is inhibited by fluoxetine, a specific blocker of 5-HT uptake and imipramine and desipramine, both are typical tricyclic antidepressants. The high affinity binding site for imipramine in this cell line has a Bmax (about 16 pmol/mg protein) which is at least 50 times higher than reported in the rat brain. Thus NCB-20 cell line is a convenient model to study the interactions between antidepressant drugs and the recognition sites for the various chemical signals participating in the transaction of communication of 5-HT synapses. This study should lead to a better knowledge of the molecular mechanisms that follows the binding of antidepressants to specific recognition sites in the target tissue.